"It may be that the order of the amino acids that make up the protein is different from anything we know of, but it can still fold up into something that looks familiar.."

is probably the most significant sentence in the entire article. Since the order of amino acids as a predictor of secondary/tertiary topography as an evolutionary guideline isn't well-plotted out by now.

^ The structure is the really important thing, but we can't get there directly yet.

Diana Gitig wrote:

They note that, besides the obvious part about a brand new DNA binding protein, their most important insight is that there are still new things out there to be discovered. Just because we know about a lot of proteins, DNA sequences, and mechanisms of transcriptional regulation, we shouldn’t get complacent and think that we know them all.

This is a rather drastic generalization of their conclusion. Obviously no one in biology thinks we have it all figured out, and no one thinks we know everything about proteins or transcription. We wouldn't be doing this research in that case.

Their real conclusion:

Lohse & Hernday et al. wrote:

Finally, the appearance of a distinctive family of sequencespeciﬁc proteins in relatively recent evolutionary history suggests that other evolutionary lineages likely contain newly formed, unannotated transcriptional regulators. We propose that the reliance on deep homology in enumerating and analyzing transcriptional regulators may have inadvertently missed those regulators most relevant to the emergence of new clades.

Translating the jargon, they're saying that our current knowledge of transcription factors is heavily based on sequence homology (that is, the sequence of the protein must match an existing factor). Finding this new TF suggests that there might be other groups of TFs out there.

Taking that paragraph to mean "gosh there's so much to explore!" is rather oversimplified.

^ The structure is the really important thing, but we can't get there directly yet.

Diana Gitig wrote:

They note that, besides the obvious part about a brand new DNA binding protein, their most important insight is that there are still new things out there to be discovered. Just because we know about a lot of proteins, DNA sequences, and mechanisms of transcriptional regulation, we shouldn’t get complacent and think that we know them all.

This is a rather drastic generalization of their conclusion. Obviously no one in biology thinks we have it all figured out, and no one thinks we know everything about proteins or transcription. We wouldn't be doing this research in that case.

Their real conclusion:

Lohse & Hernday et al. wrote:

Finally, the appearance of a distinctive family of sequencespeciﬁc proteins in relatively recent evolutionary history suggests that other evolutionary lineages likely contain newly formed, unannotated transcriptional regulators. We propose that the reliance on deep homology in enumerating and analyzing transcriptional regulators may have inadvertently missed those regulators most relevant to the emergence of new clades.

Translating the jargon, they're saying that our current knowledge of transcription factors is heavily based on sequence homology (that is, the sequence of the protein must match an existing factor). Finding this new TF suggests that there might be other groups of TFs out there.

Taking that paragraph to mean "gosh there's so much to explore!" is rather oversimplified.

You just reiterated my entire response, with about twice as many words, and with more obtuse language. Congratulations.

Thrush? So /that's/ what that smooth white sticky coating in my mouth is. Welp, looks like I'll be eating for two, now.

On a fun side note, it is usually found in either children or patients with a CD4 count of less than 400 (HIV+, late stage).

Also happens in patients being treated with powerful antibiotics but no anti-fungals.

And pretty much anyone treated with corticosteroids, oral or inhaled. Anyone with (or with kids) with asthma could tell you that.

And anyone who has recently had a prolonged period of excessively dry mouth.

Speaking as someone who just caught it after being rushed to hospital last night for severe dehydration due to a week-long battle with gastroenteritis (caused by C. Difficile, of all things...).

This has just not been my week...

As a gay man, I foresee some awkward questions during a date I had planned for tomorrow. Pity that people assume thrush == AIDS (for those who even recognize thrush, anyway). And no, I know I don't have AIDS or HIV, as I had a full lab array done, including PCR, when I was in hospital (since C. Difficile is so rare) and everything was normal (edit: not that I don't also get regularly tested, of course, but PCR can pick up HIV particles as soon as they're enter your bloodstream, so its a much better test).

"It may be that the order of the amino acids that make up the protein is different from anything we know of, but it can still fold up into something that looks familiar.."

is probably the most significant sentence in the entire article. Since the order of amino acids as a predictor of secondary/tertiary topography as an evolutionary guideline isn't well-plotted out by now.

It isn't? From a machine learning perspective, I can tell you that predicting secondary structure from amino acid sequence has pretty much been done to death by now, though tertiary (and quaternary) are still works-in-progess.

Predicting secondary structure is mostly about recognizing existing motifs--I think you're right that we're pretty decent at doing that. This particular protein might be a challenge if its sequence is really unusual. Going past secondary structure is very difficult, particularly with no homology to work off of.

altarego wrote:

You just reiterated my entire response, with about twice as many words, and with more obtuse language. Congratulations.

Except for all the stuff you didn't talk about?

You made a point about structure, which was valid and I did acknowledge it. But there's not much we can do about the structure issue right now, so we will continue to try to find other ways to identify TFs (and annotate proteins in general). A structure for this protein would be helpful in confirming that is indeed a transcription factor. Hopefully it can be crystallized.

The rest of my post was about the conclusion of the article (which I thought was vapid) and the conclusions of the paper (which were much more specific to the field). It had nothing to do with what you wrote, as you said nothing about it.

Finally, I invite you to re-read the last sentence of your post and then think more about "obtuse language".

"It can also infect other dark, moist, bodily orifices. (Especially if you spend all summer in a wet bathing suit.)" This is a science website. By all means, beat around the bush if you want to, but feel free to use the proper medical terms. Candida can infect the vagina, commonly called a yeast infection. See, wasn't that easy?

It isn't? From a machine learning perspective, I can tell you that predicting secondary structure from amino acid sequence has pretty much been done to death by now, though tertiary (and quaternary) are still works-in-progess.

But so what? Secondary structure alone won't let you answer the questions raised regarding this protein.

It isn't? From a machine learning perspective, I can tell you that predicting secondary structure from amino acid sequence has pretty much been done to death by now, though tertiary (and quaternary) are still works-in-progess.

But so what? Secondary structure alone won't let you answer the questions raised regarding this protein.

This put it more eloquently than I could. We've mapped out the free energy space of what's possible for *most* linear-secondary-tertiary constructs of amino acid sequences. If this provides a new space for polypeptides to wiggle in, then I'm more excited about *that* than whether it's for transcription factor or not.

Thrush? So /that's/ what that smooth white sticky coating in my mouth is. Welp, looks like I'll be eating for two, now.

On a fun side note, it is usually found in either children or patients with a CD4 count of less than 400 (HIV+, late stage).

Also happens in patients being treated with powerful antibiotics but no anti-fungals.

And pretty much anyone treated with corticosteroids, oral or inhaled. Anyone with (or with kids) with asthma could tell you that.

And anyone who has recently had a prolonged period of excessively dry mouth.

Speaking as someone who just caught it after being rushed to hospital last night for severe dehydration due to a week-long battle with gastroenteritis (caused by C. Difficile, of all things...).

This has just not been my week...

As a gay man, I foresee some awkward questions during a date I had planned for tomorrow. Pity that people assume thrush == AIDS (for those who even recognize thrush, anyway). And no, I know I don't have AIDS or HIV, as I had a full lab array done, including PCR, when I was in hospital (since C. Difficile is so rare) and everything was normal (edit: not that I don't also get regularly tested, of course, but PCR can pick up HIV particles as soon as they're enter your bloodstream, so its a much better test).

C. diff isn't as rare as you think it is; especially in certain populations (not necessarily yours). Which is why it's so insidious. But you can definitely ask your doc if you're also being treated with antifungals while you're being treated with antibiotics.

Predicting secondary structure is mostly about recognizing existing motifs--I think you're right that we're pretty decent at doing that. This particular protein might be a challenge if its sequence is really unusual. Going past secondary structure is very difficult, particularly with no homology to work off of.

altarego wrote:

You just reiterated my entire response, with about twice as many words, and with more obtuse language. Congratulations.

Except for all the stuff you didn't talk about?

You made a point about structure, which was valid and I did acknowledge it. But there's not much we can do about the structure issue right now, so we will continue to try to find other ways to identify TFs (and annotate proteins in general). A structure for this protein would be helpful in confirming that is indeed a transcription factor. Hopefully it can be crystallized.

The rest of my post was about the conclusion of the article (which I thought was vapid) and the conclusions of the paper (which were much more specific to the field). It had nothing to do with what you wrote, as you said nothing about it.

Finally, I invite you to re-read the last sentence of your post and then think more about "obtuse language".

Structure has very little to do with whether something is a transcription factor or not. Hell, even random protein degradation remnants can bind to DNA or RNA to control transcription or translation. My point is that we're *not* pretty decent about predicting function from primary (linear) or secondary topology of proteins.

"It can also infect other dark, moist, bodily orifices. (Especially if you spend all summer in a wet bathing suit.)" This is a science website. By all means, beat around the bush if you want to, but feel free to use the proper medical terms. Candida can infect the vagina, commonly called a yeast infection. See, wasn't that easy?

I'll keep the authors who understand that leaving side notes as minor exercises for the reader makes for better writing, thank you.

WOR3? Come on biologists, that something that a student might actually be able to remember. Astronomers routinely give new things names like PSR J0348+0432, S/2012 (134340) 1 or KOI-135 b. Much higher cognitive load on aspiring members of the field.

Back when I was first learning Biology, I remember thinking that all the encoding in DNA must be very complicated. It has to turn things on and off during development and it also seems to keep a part of evolutionary history in it. When I asked my biology teacher, he said that it had all been figured out. Well, it seem like we are a long way from doing that. It is really amazing how much variety evolution has packed into four bases (five if you include RNA) and twenty or so Amino Acids.

Has anyone looked at it from a pure information aspect? For example, how many combinations are posible, how many have been used, how are specific problems handled, etc?

"It can also infect other dark, moist, bodily orifices. (Especially if you spend all summer in a wet bathing suit.)" This is a science website. By all means, beat around the bush if you want to, but feel free to use the proper medical terms. Candida can infect the vagina, commonly called a yeast infection. See, wasn't that easy?

I'll keep the authors who understand that leaving side notes as minor exercises for the reader makes for better writing, thank you.

It's not better writing when the "excercise for the reader" version is more verbose than the alternative.

"It can also infect other dark, moist, bodily orifices. (Especially if you spend all summer in a wet bathing suit.)" This is a science website. By all means, beat around the bush if you want to, but feel free to use the proper medical terms. Candida can infect the vagina, commonly called a yeast infection. See, wasn't that easy?

I'll keep the authors who understand that leaving side notes as minor exercises for the reader makes for better writing, thank you.

It's not better writing when the "excercise for the reader" version is more verbose than the alternative.

No kidding. "Exercise for the reader" normally means leave something out to save space, not replace a single word that you aren't mature enough to say with 16 other words.